Background. In the U.S., men who have sex with men (MSM) who engage in transactional sex (i.e., sex work) are a largely understudied group at particularly elevated risk for mental health problems, including drug abuse, and HIV infection. Sex work has been associated with elevated HIV sexual risk-taking and/or seroprevalence among MSM1; 2. MSM represent the population of individuals with the largest number of new infections (>50%) domestically and almost half of all Americans living with HIV (49%)3, 4. This proposal builds on our formative work with MSM sex workers in Boston, which revealed that the majority (69%) reported at least one episode of unprotected serodiscordant anal sex (either insertive or receptive) with a mean of 11 (SD=42) male sex partners of different HIV serostatus, and an average of 46 (SD=65) total sex work partners in the past 12 months5. Almost one third (31%) were HIV-infected, and most (84%) had a steady male or female partner, thus the risk for HIV-infection/transmission is not only to/from their sex work clients but also to/from their primar partners. Notably, every participant reported using a variety of drugs and/or alcohol in the context of sex work in the prior 12 months. This formative qualitative work, however, enrolled a relatively small sample (N=32). In order to be effective, future HIV prevention and substance abuse treatment interventions for this at risk, marginalized group need to be based on a better understanding of the social/sexual network characteristics and their relationship to drug and alcohol abuse, HIV risk behaviors and the varied psychosocial and socio-economic complexities of MSM sex workers. Overview of project. We propose to conduct a longitudinal epidemiological assessment of a sample (N = 140) of MSM sex worker networks in Massachusetts to identify protective and risk factors that affect HIV transmission dynamics longitudinally. We will recruit a diverse cohort of MSM sex workers to complete an in- person comprehensive social, sexual, and drug network, sexual risk, substance use, and psychosocial assessment battery at 3 time points during study follow-up. Longitudinal data will enhance our understanding of how contemporary social, sexual, and drug abuse network characteristics contribute to increased HIV and STI spread among MSM sex workers. We will also conduct HIV and STI testing during the 3 in-person assessment visits spanning a 12 month period. Finally, the information gained will be used to develop a simulation model to examine which prevention modality (e.g., network-based, conditional cash transfer, PrEP, etc) would impact decreased HIV incidence most successfully among this group. As a whole, these results will serve to inform a culturally appropriate, drug/alcohol abuse treatment/prevention and/or HIV prevention intervention for this high-risk subpopulation of MSM.